tbuckley/cabot-search huggingface dataset:
Abstract LB157: Prevalence of metabolic syndrome among cancer survivors in the US
Authors: Adaora Ezeani, Tanya Agurs-Collins
Journal: Cancer Research (2022)

Abstract Background: The purpose of this study was to determine the prevalence of metabolic syndrome (MetS) and its components in cancer survivors (CS) compared to participants without a history of cancer who have at least one chronic disease (CD) and those without a chronic disease diagnosis (NCD). Methods: Using National Health and Nutrition Examination Survey (NHANES) data from 2015 to 2018, the prevalence MetS was evaluated among participants 50 years and older (n= 5466). MetS was defined based on the National Cholesterol Education Program’s Adult Treatment Panel III. Weighted data were used to estimate the prevalence of MetS, stratified by cancer site, gender, sex, and race/ethnicity. Chi-square test and logistic regression was used to assess group comparisons and associations respectively. Results: Prevalence of MetS was higher among CS (71.4%) and CD (75.1%) participants compared to NCD (45.7%). Compared to NCD, participants with uterine cancer (UCa) and non-melanoma skin cancer (nMSC) had higher odds of MetS, with and without adjusting for covariates (p&amp;lt;0.05). Those with UCa had the highest odds of MetS (OR 3.49, CI 1.51 - 8.06, p&amp;lt;0.01) among all cancer types and NCD respondents. Regarding individual components of MetS, PCa survivors had lower odds of having elevated WC (p&amp;lt;0.01) and BrCa and UCa had higher odds of having elevated WC (p&amp;lt;0.05) after adjusting for covariates, compared to NCD. nMSC had higher odds of reduced HDL, elevated TG, and elevated WC (p&amp;lt;0.05) after adjusting for covariates. Conclusions: This study indicates that UCa and nMSC survivors have a strong association with MetS. In particular, nMSC survivors demonstrated statistically significant odds of meeting 3 of the 5 risk factors for MetS after adjusting for confounding variables. A better understanding of the association between MetS, its components, and specific cancers can provide insight into providing complete clinical care to CS. Citation Format: Adaora Ezeani, Tanya Agurs-Collins. Prevalence of metabolic syndrome among cancer survivors in the US [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB157.
Abstract 1718: Characterization of infiltrating immune cells after irradiation using 10x genomics single cell sequencing
Authors: Frida Ponthan, Valentina Ubertini, Gary Beale
Journal: Cancer Research (2022)

Abstract Background: Radiation therapy is delivered to approximately 50% of all cancer patients. It has long been known that radiation causes not only DNA strand breaks, apoptosis, and necrosis, but also immunogenic modulation. Lately, there has been renewed interest in the potential of irradiation in colorectal cancer, not only as an adjuvant and palliative treatment, but also as an immune stimulant. Materials and Methods: CT26 murine colorectal carcinoma cells were subcutaneously implanted on the flank of BALB/c mice. Tumors were exposed to sham, single dose or fractionated radiotherapy regimens via a 300kV, 10mA X-ray with additional filtration to give a radiation quality of 2.3mm Cu half-value layer (HVL). Mice were anaesthetized, restrained and delivered a single uniform dose of radiation at a rate of 0.696Gy/min with the whole mouse being lead shielded except for a 1cm hole in the lead above the tumor site. Tumors were harvested at different timepoints post irradiation and dissociated into single cell suspensions. The tumor microenvironment and immune response within the tumors were analyzed with flow cytometry comparing the different treatment regimens. The individual CD45+ cell profile was investigated using 10x gene expression. 10x sequencing was demultiplexed using CellRanger and data analyzed using Seurat and ACTINN. Results: Following the initial cytotoxicity, flow cytometry showed a clear immune stimulatory effect of radiotherapy with immune cells infiltrating the irradiated tumors. The level of infiltration was dependent on the treatment scheduling. For single cell assessments, we observed approximately 8000 reads/cell and T-SNE cluster analysis using Seurat identified 16 clusters in control and treated samples. Identification of clusters by ACTINN demonstrated that CD8+ T-cells were increased 8-fold in irradiated samples whereas monocytes numbers decreased 3-fold. In irradiated tumors, the main population of CD8+ T-cells with increased numbers also expressed NKG7. Conclusion: These data provide evidence that radiotherapy can enhance immune cell trafficking to locally treated CT26 tumors. Furthermore, 10x genomics single cell sequencing revealed increased levels of cytotoxic T-cells expressing NKG7, a protein implicated in enhanced killing of extracellular targets. This response could prime the tumors such that they may be exploited by immune modulating drugs. Citation Format: Frida Ponthan, Valentina Ubertini, Gary Beale. Characterization of infiltrating immune cells after irradiation using 10x genomics single cell sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1718.
Abstract 2236: A novel integrated predictive model for pancreatic cancer
Authors: Temin Ke, Artitaya Lophatananon, Kenneth Muir, Xinzhu Yu
Journal: Cancer Research (2022)

Abstract Background: Pancreatic cancer is the 7th leading cause of cancer-related mortality and the 12 th most common cancer globally. Many studies have identified risk factors for pancreatic cancer, nevertheless, there have been few combined risk factor models developed for the UK specific population. Due to the high incidence with a poor survival rate together with the potential high preventable rate, it is important to establish an accessible predictive risk factor model for identifying potential high-risk populations. Study aim: To establish a pancreatic cancer risk prediction model by integrating the current risk factors together with established genomic biomarkers. Method:Using data from the UK biobank we have investigated the role of established and suggested risk factors for pancreatic cancer. The established risk factors include age, BMI, smoking, alcohol consumption, diabetes and pancreatitis. We also calculate the added prediction from the current polygenic risk score (PRS) to evaluate the risk for genetic predisposition. Last, we utilise the multivariate logistic regression models to establish a novel risk model by integrating the well-known risk factors such as cigarette smoking, heavy alcohol consumption, increased BMI, chronic pancreatitis, diabetics, some germline mutation, and our new evaluated PRS and biological clocks. Results: We will present the performance of the novel integrated model which will be useful for use in primary care to identify the at-risk population. This will assist in the promotion of prevention recommendations and for future health check follow-up. Citation Format: Temin Ke, Artitaya Lophatananon, Kenneth Muir, Xinzhu Yu. A novel integrated predictive model for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2236.
Abstract LB547: Ultra-deep targeted sequencing of circulating tumor DNA with colorectal cancer patients for prediction of treatment response and post-surgical follow-up
Authors: Hyeonah Lee, Doo A Kim, Jieun Seo, Saeam Shin, Han Sang Kim, Joong Bae Ahn, Seung-Tae Lee, Jong Rak Choi
Journal: Cancer Research (2022)

Abstract Purpose: Colorectal cancer (CRC) patients require effective biomarkers to evaluate treatment efficacy and monitor minimal residual disease. However, current monitoring tools such as tumor markers and imaging methods have limited prognostic performance. Circulating-tumor DNA (ctDNA) could be a useful biomarker for monitoring patients with CRC. In this study, we evaluated the targeted next-generation sequencing (NGS) panel using ctDNA in monitoring clinical decision-making in CRC. Experimental Design: We prospectively enrolled 100 CRC patients and collected 197_ plasma samples. Specimens were collected post-surgery from 74 patients, 42 of whom were also monitored during the immediate post-surgery and adjuvant therapy follow-up. Twenty-six patients’ bloods were received after adjuvant therapy without surgery. A total of patients performed ultra-deep sequencing of CRC-related 14 genes respectively and matched with tissue samples at the time of blood collection as possible. NGS results were assessed correlation with clinicopathologic characteristics and clinical outcome. Results: Levels of ctDNA measurements were correlated with tumor stage. Stage IV patients had significantly higher ctDNA concentration than Stage I patients. ctDNA testing detected 112 alterations in 14 genes were identified in 69% of the patients (n=100). The results showed that APC (29%), TP53 (25%), KRAS (19%), and EGFR (5%) were the most frequently mutated genes. RAS family gene mutations were detected in 37 patients, yielding a concordance of 89% with tissue samples. Also, ctDNA detection was found to be a greater predictive performance when compared with CEA. Dynamics of ctDNA mutation levels reflected five follow-up patients’ clonal evolution and clinical outcomes. These data showed ctDNA is a sensitive monitoring biomarker for any clinical condition of the patients. Conclusions: The present study suggests that the use of ctDNA in CRC patients can be a valuable non-invasive monitoring tool for monitoring disease states during or after treatment. Serial ctDNA testing can contribute to improving patient management through monitoring disease progression and clonal evolution. Citation Format: Hyeonah Lee, Doo A Kim, Jieun Seo, Saeam Shin, Han Sang Kim, Joong Bae Ahn, Seung-Tae Lee, Jong Rak Choi. Ultra-deep targeted sequencing of circulating tumor DNA with colorectal cancer patients for prediction of treatment response and post-surgical follow-up [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB547.
Trends in Health Care Use Among Black and White Persons in the US, 1963-2019
Authors: Samuel L. Dickman, Adam Gaffney, Alecia McGregor, David U. Himmelstein, Danny McCormick, David H. Bor, Steffie Woolhandler
Journal: JAMA Network Open (2022)

<h3>Importance</h3> In the US, Black people receive less health care than White people. Data on long-term trends in these disparities, which provide historical context for interpreting contemporary inequalities, are lacking. <h3>Objective</h3> To assess trends in Black-White disparities in health care use since 1963. <h3>Design, Setting, and Participants</h3> This cross-sectional study analyzed 29 US surveys conducted between 1963 and 2019 of noninstitutionalized Black and non-Hispanic White civilians. <h3>Exposures</h3> Self-reported race and ethnicity. <h3>Main Outcomes and Measures</h3> Annual per capita visit rates (for ambulatory, dental, and emergency department care), inpatient hospitalization rates, and total per capita medical expenditures. <h3>Results</h3> Data from 154 859 Black and 446 944 White (non-Hispanic) individuals surveyed from 1963 to 2019 were analyzed (316 503 [52.6%] female; mean [SD] age, 37.0 [23.3] years). Disparities narrowed in the 1970s in the wake of landmark civil rights legislation and the implementation of Medicare and Medicaid but subsequently widened. For instance, the White-Black gap in ambulatory care visits decreased from 1.2 (95% CI, 1.0-1.4) visits per year in 1963 to 0.8 (95% CI, 0.6-1.0) visits per year in the 1970s and then increased, reaching 3.2 (95% CI, 3.0-3.4) visits per year in 2014 to 2019. Even among privately insured adults aged 18 to 64 years, White individuals used far more ambulatory care (2.6 [95% CI, 2.4-2.8] more visits per year) than Black individuals in 2014 to 2019. Similarly, White peoples’ overall health care use, measured in dollars per capita, exceeded that of Black people in every year. After narrowing from 1.96 in the 1960s to 1.26 in the 1970s, the White-Black expenditure ratio began widening in the 1980s, reaching 1.46 in the 1990s; it remained between 1.31 and 1.39 in subsequent periods. <h3>Conclusions and Relevance</h3> This study’s findings indicate that racial inequities in care have persisted for 6 decades and widened in recent years, suggesting the persistence and even fortification of structural racism in health care access. Reform efforts should include training more Black health care professionals, investments in Black-serving health facilities, and implementing universal health coverage that eliminates cost barriers.
Abstract 3284: HB-201 and HB-202, an arenavirus-based immunotherapy, induces tumor T cell infiltration in patients with HNSCC and other HPV16+ tumors
Authors: Donna Edwards, Michael Schwendinger, Kia Katchar, Katia Schlienger, Klaus Orlinger, Igor Matushansky, Henning Lauterbach
Journal: Cancer Research (2022)

Abstract Background: Human Papillomavirus 16 (HPV16) is the most common etiologic agent of HPV-associated cancers. Treatment options are limited for patients with HPV16+ recurrent or metastatic cancers. HPV16 E7 and E6 oncogenes constitute attractive immunotherapeutic targets. HB-201 and HB-202 are live-attenuated replicating vectors based on LCMV and PICV arenaviruses, respectively, that express the same non-oncogenic HPV16 E7E6 fusion protein for induction of tumor specific T cell responses. Methods: A Phase I/II open labelled clinical trial of HB-201 single vector therapy and HB-202/HB-201 alternating two-vector therapy in patients with treatment-refractory HPV16+ cancers is currently ongoing (NCT04180215). To assess circulating E6/E7 specific T cell responses, IFN-γ enzyme-linked immunospot (ELISpot) and intracellular cytokine staining were performed on pre- and post-treatment peripheral blood mononuclear cells (PBMCs). Evaluation of T cell infiltration and PD-L1 status in tumor bed was performed on paired tissue biopsies from a subset of patients by multiplex immunofluorescence. Results: Single vector therapy (HB-201) and alternating two-vector therapy (HB-202/HB-201) rapidly induce high E6/E7 specific T cell levels, reaching up to ~40% of the circulating CD8+ T cell pool. Alternating two-vector therapy seems to maintain E6/E7 specific T cell responses better in continuous dosing compared to single vector therapy. Furthermore, we demonstrate tumor tissue T cell infiltration in more than 50% of patient samples analyzed. Currently, in depth sequencing of paired biopsies is underway to characterize the tumor microenvironment in response to HB-201 and HB-202/HB-201 treatment. Conclusion: In this updated dataset, we show that HB-201 and HB-202/HB-201, rapidly induce unprecedented E6/E7 specific T cell levels in circulation following a single dose. Furthermore, these data are seen in conjunction with a pronounced increase of post-treatment CD8+ T cells in tumor, suggesting E6/E7 specific T cell infiltration. Our arenavirus vectors expressing the E7E6 fusion antigen demonstrate an attractive and safe therapy for patients with treatment refractory HPV16+ cancers. The ability of replicating arenavirus vectors to incorporate a broad range of antigens and the potent T cell inducing capacity provide a strong rationale to apply this novel therapy to other cancers. Citation Format: Donna Edwards, Michael Schwendinger, Kia Katchar, Katia Schlienger, Klaus Orlinger, Igor Matushansky, Henning Lauterbach. HB-201 and HB-202, an arenavirus-based immunotherapy, induces tumor T cell infiltration in patients with HNSCC and other HPV16+ tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3284.
Abstract 1965: Complete remission in advanced epithelial ovarian cancer is predicted by metabolic signatures measured in the media of patient’s primary culture 3D tumor explants: A metabolomic analysis
Authors: Adam J. Nagourney, Paulo D'Amora, Ismael Dale Cotrim Guerreiro Silva, Steven S. Evans, Robert A. Nagourney
Journal: Cancer Research (2022)

Abstract Ovarian cancer is the leading cause of gynecologic cancer death with over 21,000 new diagnosis and 13,000 deaths each year in the US. Treatment with platinum-based chemotherapy induces remission in up to 80% of patients yet the majority relapse and die from their disease within 5 years. We recently reported the analysis of patients with advanced ovarian cancers using plasma metabolomics to predict response and survival (D’Amora et al Gynecol Oncol, October 2021). As part of that study human tumor explants were submitted for the measurement of platinum resistance by ex vivo analysis of programmed cell death (EVA/PCD࣪). Media obtained from the non-drug exposed control cultures were examined by mass spectrometry for the quantification of 186 individual metabolites using the Biocrates’ p180 platform. Results obtained with the tissue culture media identify biochemical signatures that correlate with the achievement of complete pathologic remission. Among the most discrimination findings were the media concentrations of phosphatidyl choline (PC) aa c42:0 and the ratio of (PC) aa C40:2 divided by (PC) ae C42:1 suggesting either hyperactivity of lipid elongases or defective beta oxidation of very long chain fatty acids in drug refractory patients. When we compared the results of 8 patients who achieved pCR with 3 patients with residual disease the aa C42:0 concentration and the ratio aa C42:0/ae C42:1 provided an AUC= 0.958 (p. &amp;lt; 0.01) The findings suggest that peroxisomal dysfunction leads to the accumulation of very long chain fatty acid lipids. These species are known to induce endoplasmic reticulum and oxidative stress and are associated with the neurodegenerative diseases like Zellweger syndrome. We have reported similar findings in drug refractory breast cancer patients (da Silva et al, Oncotarget, August Aug 2018) suggesting common lipid metabolic changes in drug resistant adenocarcinomas. The results of these analyses could provide prognostic and predictive information for patients diagnosed with advanced epithelial ovarian cancers. Further studies correlating these findings with plasma metabolic signatures are underway as will be reported. Citation Format: Adam J. Nagourney, Paulo D'Amora, Ismael Dale Cotrim Guerreiro Silva, Steven S. Evans, Robert A. Nagourney. Complete remission in advanced epithelial ovarian cancer is predicted by metabolic signatures measured in the media of patient’s primary culture 3D tumor explants: A metabolomic analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1965.
Abstract 1797: Bcl-2 up-regulation mediates taxane resistance downstream of APC loss
Authors: Sara Maloney, Sarah Zabala, Grace Richmond, Jenifer R. Prosperi
Journal: Cancer Research (2022)

Abstract Patients with triple negative breast cancer (TNBC) are treated with traditional chemotherapy, such as paclitaxel (PTX). Despite the efficacy of taxanes, many tumors will recur due to drug resistance. Therefore, the need to understand the mechanism behind drug resistance is critical to improve patient outcome and survival. Our lab was the first to show that loss of the Adenomatous Polyposis Coli (APC) tumor suppressor caused resistance to PTX in the MDA-MB-157 human TNBC cell line. In the absence of APC, apoptosis induction was decreased, as measured through cleaved caspase 3 and annexin/PI staining. To understand the molecular mechanisms behind APC-mediated PTX response, we analyzed the BCL-2 family of proteins and found a robust increase of the pro-survival family member, Bcl-2. The BH3 mimetic, ABT-199 (Venetoclax), which specifically targets Bcl-2, has been used as a single or combination therapy in multiple hematologic malignancies. In addition, ABT-199 has shown promise in multiple subtypes of breast cancer. Therefore, we used ABT-199 in combination with PTX to address the hypothesis that APC-induced Bcl-2 increase is responsible for PTX resistance. Combination treatment in three CRISPR-mediated APC knockout TNBC cell lines (MDA-MB-157, MDA-MB-231, and SUM159) caused changes in cell proliferation and apoptosis. Combined, these data suggest restored sensitivity to PTX using ABT-199. Our studies are the first to show that Bcl-2 inhibition can restore PTX-sensitivity in APC mutant breast cancer cells. These studies are critical to advance better treatment regimens in patients with TNBC. Citation Format: Sara Maloney, Sarah Zabala, Grace Richmond, Jenifer R. Prosperi. Bcl-2 up-regulation mediates taxane resistance downstream of APC loss [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1797.
Mobile health school screening and telemedicine referral to improve access to specialty care in rural Alaska: a cluster- randomised controlled trial
Authors: Susan D Emmett, Alyssa Platt, Elizabeth L Turner, Joseph J Gallo, Alain B Labrique, S Meade Inglis, Cole D Jenson, Heather E Parnell, Nae-Yuh Wang, Kelli L Hicks, Joseph R Egger, Peter F Halpin, Michael Yong, Jeromie Ballreich, Samantha Kleindienst Robler
Journal: The Lancet Global Health (2022)

School-based programmes, including hearing screening, provide essential preventive services for rural children. However, minimal evidence on screening methodologies, loss to follow-up, and scarcity of specialists for subsequent care compound rural health disparities. We hypothesised telemedicine specialty referral would improve time to follow-up for school hearing screening compared with standard primary care referral.In this cluster-randomised controlled trial conducted in 15 rural Alaskan communities, USA, we randomised communities to telemedicine specialty referral (intervention) or standard primary care referral (control) for school hearing screening. All children (K-12; aged 4-21 years) enrolled in Bering Straight School District were eligible. Community randomisation occurred within four strata using location and school size. Participants were masked to group allocation until screening day, and assessors were masked throughout data collection. Screening occurred annually, and children who screened positive for possible hearing loss or ear disease were monitored for 9 months from the screening date for follow-up. Primary outcome was the time to follow-up after a positive hearing screen; analysis was by intention to treat. The trial was registered with ClinicalTrials.gov, NCT03309553.We recruited participants between Oct 10, 2017, and March 28, 2019. 15 communities were randomised: eight (750 children) to telemedicine referral and seven (731 children) to primary care referral. 790 (53·3%) of 1481 children screened positive in at least one study year: 391 (52∤1%) in the telemedicine referral communities and 399 (50∤4%) in the primary care referral communities. Of children referred, 268 (68·5%) in the telemedicine referral communities and 128 (32·1%) in primary care referral communities received follow-up within 9 months. Among children who received follow-up, mean time to follow-up was 41·5 days (SD 55·7) in the telemedicine referral communities and 92·0 days (75·8) in the primary care referral communities (adjusted event-time ratio 17·6 [95% CI 6·8-45·3] for all referred children). There were no adverse events.Telemedicine specialty referral significantly improved the time to follow-up after hearing screening in Alaska. Telemedicine might apply to other preventive school-based services to improve access to specialty care for rural children.Patient-Centered Outcomes Research Institute.